Non-Kinase Assay Services
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Background
While Protein Kinase Inhibitors (PKIs) are a cornerstone of modern drug discovery, an exclusive focus on their intended targets is a critical oversight. The long-held assumption that the multi-target activity of PKIs is confined to the kinome has been proven incorrect. A landmark, large-scale analysis has definitively shown that hundreds of well-characterized PKIs also demonstrate high-confidence activity against over 200 non-kinase targets, including crucial epigenetic regulators and metabolic enzymes.
To truly understand a compound's Mechanism of Action (MoA), predict its efficacy, and build a robust safety profile, researchers need to investigate these non-kinase interactions. At Creative Biolabs, with over two decades of experience guiding drug discovery programs, we provide the comprehensive non-kinase assay suites necessary to illuminate these critical off-target effects, turning potential liabilities into therapeutic opportunities.
Fig.1 The classification of non-protein kinase targets.1
Non-Kinase Assay Services at Creative Biolabs
To address the complex challenge of characterizing total cellular activity, Creative Biolabs offers a robust platform of non-kinase assay services. Our mission is to provide our clients with a holistic understanding of their compounds, moving beyond a singular focus on the primary target. This comprehensive profiling is essential for making informed decisions, de-risking candidates early, and uncovering novel therapeutic potential that would otherwise remain hidden.
Comprehensive Service Content: A Multi-Faceted Approach to Cellular Interrogation
Our expertise covers a vast landscape of critical non-kinase targets. We have curated panels and develop bespoke assays for key enzyme families and cellular processes, utilizing state-of-the-art technologies to ensure sensitivity and accuracy.
Helicase Assay Service
Helicases are essential motor proteins that unwind nucleic acid structures and are fundamental to DNA replication, repair, and recombination. Targets such as WRN, BLM, and RECQL4 have emerged as premier therapeutic targets in cancers with specific genetic vulnerabilities. Creative Biolabs provides advanced biochemical assays, including fluorescence-based DNA unwinding assays and ATP-hydrolysis assays, alongside cellular assays in custom-engineered cell lines to assess compound efficacy and selectivity against a panel of helicases.
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Phosphatase Assay Service
Protein phosphatases are the critical "off-switches" in signaling cascades, acting as functional counterparts to kinases. Their deregulation is a hallmark of many diseases, including cancer, metabolic disorders, and autoimmune conditions, making them a vital class of drug targets. Creative Biolabs provides comprehensive profiling against a wide array of phosphatases. Our services utilize sensitive detection methods, such as fluorescence intensity (FI) with specific substrates, to precisely quantify a compound's inhibitory or activating effects. We cover all major families, including Protein Tyrosine Phosphatases (PTPs like PTP-1B, SHP2), Serine/Threonine Phosphatases (e.g., PP1, PP2A), and dual-specificity phosphatases, providing the crucial data needed to understand a compound's impact on these key regulatory nodes.
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Protease Assay Service
Proteases are central to nearly every biological process, from digestion to apoptosis and cell migration. Unintended inhibition can lead to significant toxicity. We offer robust platforms to screen for inhibitory activity against various protease families (e.g., serine, cysteine, matrix metalloproteinases) to identify liabilities and potential new therapeutic activities.
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Histone Deacetylase (HDAC) Assay Service
HDACs remove acetyl groups from histones and other proteins, typically leading to transcriptional repression. As key epigenetic regulators, unintended modulation of these enzymes can have profound effects. Our fluorescence intensity (FI)-based assays provide precise, quantitative measurements of inhibitory activity against all classes of HDACs, enabling isoform-specific profiling.
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Lysine Acetyltransferase (KAT) Assay Service
Acting opposite to HDACs, KATs (also known as HATs) acetylate lysine residues, a mark generally associated with transcriptional activation. Characterizing activity against KATs is crucial for understanding the full epigenetic impact of a compound. We offer robust assay platforms to determine inhibitor potency and selectivity.
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Deubiquitinating Enzyme (DUB) Assay Service
The ubiquitin-proteasome system is vital for protein homeostasis. DUBs reverse ubiquitination, rescuing proteins from degradation and regulating numerous cellular processes. With over 100 DUBs in humans, they represent a major, largely untapped class of drug targets. We provide activity-based assays to screen compounds against panels of DUBs, identifying novel regulators of protein stability.
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Poly (ADP-ribose) Polymerase (PARP) Assay Service
PARP enzymes, particularly PARP1, are central to the DDR, sensing DNA breaks and signaling for their repair. Our services include highly sensitive enzymatic assays to determine IC50 values and mechanistic studies to understand binding kinetics. Critically, we also offer cellular PARP trapping assays, which measure the trapping of PARP on DNA—a key mechanism for the clinical efficacy of PARP inhibitors.
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Poly (ADP-ribose) Glycohydrolase (PARG) Assay Service
As the primary enzyme responsible for catabolizing poly (ADP-ribose) chains, PARG acts in opposition to PARP. Inhibition of PARG represents an alternative and potentially synergistic approach to targeting the DDR. We provide robust enzymatic assays to screen for and characterize PARG inhibitors, enabling a dual-pronged investigation into this critical pathway.
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Sirtuin (SIRT) Assay Service
Sirtuins are a unique class of NAD+-dependent deacetylases (Class III HDACs) that link cellular metabolism directly to protein deacetylation and gene regulation. They are implicated in aging, metabolic diseases, and cancer. Our specialized assays can determine compound activity against all seven human sirtuins (SIRT1-7), distinguishing them from classical HDAC inhibitors.
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Phosphodiesterase (PDE) Assay Service
PDEs are crucial regulators of second messenger signaling, controlling cellular levels of cAMP and cGMP. Their inhibition has led to blockbuster drugs for a range of indications. We provide assays to assess off-target interactions and primary activity against the full family of PDE enzymes, helping to predict effects on cardiovascular, inflammatory, and neurological pathways.
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Protein Phosphatase (PP) Assay Service
As the functional counterparts to kinases, phosphatases are critical for switching off signaling pathways and are themselves important drug targets. Aberrant phosphatase activity is linked to numerous diseases. Our FI-based assays can precisely quantify a compound's inhibitory or activating effect on a wide range of protein phosphatases, including PTPs, Ser/Thr phosphatases, and dual-specificity phosphatases.
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Benefits for You
Choosing an assay partner is a critical decision. At Creative Biolabs, our value is built on three pillars:
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Unmatched Scientific Expertise
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A Systematic, Unbiased Approach
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Cutting-Edge, Customizable Technology
FAQs
Q1: My compound is a highly selective kinase inhibitor. Why do I need non-kinase profiling?
A1: Recent large-scale studies provide definitive evidence that even the most selective PKIs can possess potent activity against functionally unrelated non-kinase targets. This off-target activity can be central to a drug's therapeutic efficacy (beneficial polypharmacology) or the source of unexpected toxicity. Profiling against non-kinase targets is a critical step in de-risking your candidate and fully understanding its biological impact.
Q2: Can you develop a custom assay for a novel or uncharacterized non-kinase target?
A2: Yes. This is a core strength at Creative Biolabs. Our R&D team excels at developing and validating novel biochemical and cell-based assays from the ground up. We partner with you to understand the target biology and build a robust assay cascade, from initial tool compound validation to screening and profiling of your lead candidates.
Q3: What is the typical process for initiating a project with Creative Biolabs?
A3: The process begins with a confidential, in-depth scientific consultation with our experts. We discuss your compound, your primary targets, and your research objectives. Based on this, we develop a tailored project proposal outlining the recommended assay strategy, timelines, and deliverables. We prioritize clear communication and a collaborative approach from start to finish.
Contact Us
The hidden interactions of your compound could hold the key to its success or the cause of its failure. Don't leave it to chance. Partner with the experts at Creative Biolabs to gain a complete understanding of your drug's mechanism and navigate your path to the clinic with confidence. To discuss your project with a Creative Biolabs scientific expert, please contact us today.
Reference
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Mobasher, Mona et al. "Comprehensive Data-Driven Assessment of Non-Kinase Targets of Inhibitors of the Human Kinome." Biomolecules vol. 14,3 258. 21 Feb. 2024. DOI: 10.3390/biom14030258. Distributed under Open Access License CC BY 4.0, without modification.
For Research Use Only | Not For Clinical Use
